Chimaeric anti-CD4 monoclonal antibody cross-linked by monocyte Fcγ receptor mediates apoptosis of human CD4 lymphocytes

Previous studies have shown that murine anti-CD4 monoclonal antibody, cross-linked by rabbit anti-mouse immunoglobulin, could mediate apoptosis of murine CD4⁺ lymphocytes when they were stimulated by T cell receptor antibody. In this study, we have shown that the murine anti-CD4 monoclonal antibody, OKT4, can induce apoptosis in human CD4⁺ T cells stimulated by the recall antigen tuberculin purified protein derivative (PPD) only when cross-linked by rabbit anti-mouse immunoglobulin. The chimeric anti-CD4 monoclonal antibody, cM-T412 whose Fc fragment is human, was able to cause apoptosis without cross-linking by a second antibody. Similarly, abolition of PPD-induced proliferation of peripheral blood mononuclear cells by cM-T412 did not require cross-linking with rabbit anti-human immunoglobulin. Inhibition of proliferation by cM-T412 could be reduced by pre-treating monocytes with heat-aggregated human IgG. This suggested that monocyte Fcγ receptors might be cross-linking the human Fc of cM-T412. Propidium iodide staining together with immunofluorescence showed that the apoptotic cells were indeed CD4⁺ lymphocytes. It is proposed that during treatment with cM-T412 in autoimmune disease such as rheumatoid arthritis, cM-T412-coated CD4 T cells, when they are subsequently stimulated by the unknown arthritogenic antigen, may undergo apoptotic cell death through cross-linking of cM-T412 on Fey receptor-positive cells within the joint.     

Theophylline and fibrocystic breast disease

After literature reports linking fibrocystic breast disease (FBD) to methylxanthine ingestion, a pilot study was undertaken to investigate the possible contribution of theophylline to this effect. The major goal of this project was to measure the effect of theophylline therapy on FBD in asthmatic women. All women attending an allergy clinic or an obstetrics/gynecology clinic over a 9-month period were examined to clinically assess FBD and were asked to complete a detailed questionnaire covering health history, other risk factors, and drug and dietary methylxanthines. The sample included 62 asthmatic women, 66 allergic but not asthmatic women, and 72 nonallergic and nonasthmatic women. By use of the FBD clinical taxonomy with its 19-point scale going from 0 to 18 that was developed for this study, the three groups did not differ significantly in terms of mean severity of FBD. On analyzing the effect of each of the methylxanthines on FBD severity, there is clear evidence that total methylxanthines was a contributing factor in FBD severity with or without adjustment for relevant variables, such as age, menopause, pregnancies, and groups. Theophylline was significant only when adjustments were made for age, pregnancy, and menopause in contrast to caffeine that was only significant with no adjustments.     

Coxsackievirus B3-associated myocardial pathology and viral load reduced by recombinant soluble human decay-accelerating factor in mice

Coxsackievirus B3 (CVB3) infection can result in myocarditis, which in turn may lead to a protracted immune response and subsequent dilated cardiomyopathy. Human decay-accelerating factor (DAF), a binding receptor for CVB3, was synthesized as a soluble IgG1-Fc fusion protein (DAF-Fc). In vitro, DAF-Fc was able to inhibit complement activity and block infection by CVB3, although blockade of infection varied widely among strains of CVB3. To determine the effects of DAF-Fc in vivo, 40 adolescent A/J mice were infected with a myopathic strain of CVB3 and given DAF-Fc treatment 3 days before infection, during infection, or 3 days after infection; the mice were compared with virus alone and sham-infected animals. Sections of heart, spleen, kidney, pancreas, and liver were stained with hematoxylin and eosin and submitted to in situ hybridization for both positive-strand and negative-strand viral RNA to determine the extent of myocarditis and viral infection, respectively. Salient histopathologic features, including myocardial lesion area, cell death, calcification and inflammatory cell infiltration, pancreatitis, and hepatitis were scored without knowledge of the experimental groups. DAF-Fc treatment of mice either preceding or concurrent with CVB3 infection resulted in a significant decrease in myocardial lesion area and cell death and a reduction in the presence of viral RNA. All DAF-Fc treatment groups had reduced infectious CVB3 recoverable from the heart after infection. DAF-Fc may be a novel therapeutic agent for active myocarditis and acute dilated cardiomyopathy if given early in the infectious period, although more studies are needed to determine its mechanism and efficacy.     

The absence of a B allele in acquired B blood group phenotype confirmed by a DNA based genotyping method.

A case of an 87 year old woman with carcinomatous sigmoid colon, found to be of group A1 with acquired B status, is reported. The acquired B phenotype was confirmed by the absence of a B allele in the patient using denaturing gradient gel electrophoresis of a DNA fragment amplified from the ABO locus by the polymerase chain reaction.     

Monkeypox virus detection in rodents using real-time 3'-minor groove binder TaqMan assays on the Roche LightCycler

During the summer of 2003, an outbreak of human monkeypox occurred in the Midwest region of the United States. In all, 52 rodents suspected of being infected with monkeypox virus were collected from an exotic pet dealer and from private homes. The rodents were euthanized and submitted for testing to the United States Army Medical Research Institute of Infectious Diseases by the Galesburg Animal Disease Laboratory, Illinois Department of Agriculture. The rodent tissue samples were appropriately processed and then tested by using an integrated approach involving real-time polymerase chain reaction (PCR) assays, an antigen-detection immunoassay, and virus culture. We designed and extensively tested two specific real-time PCR assays for rapidly detecting monkeypox virus DNA using the Vaccinia virus F3L and N3R genes as targets. The assays were validated against panels of orthopox viral and miscellaneous bacterial DNAs. A pan-orthopox electrochemiluminescence (ECL) assay was used to further confirm the presence of Orthopoxvirus infection of the rodents. Seven of 12 (58%) animals (seven of 52 (15%) of all animals) tested positive in both monkeypox-specific PCR assays and two additional pan-orthopox PCR assays (in at least one tissue). The ECL results showed varying degrees of agreement with PCR. One hamster and three gerbils were positive by both PCR and ECL for all tissues tested. In addition, we attempted to verify the presence of monkeypox virus by culture on multiple cell lines, by immunohistology, and by electron microscopy, with negative results. Sequencing the PCR products from the samples indicated 100% identity with monkeypox virus strain Zaire-96-I-16 (a human isolate from the Congo). These real-time PCR and ECL assays represent a significant addition to the battery of tests for the detection of various orthopoxviruses. In light of the recent monkeypox virus transmissions, early detection of the virus is crucial for both natural outbreaks and potential acts of bioterrorism.     

On-line respiratory artefact removal via adaptive FIR filters in rheopneumographic measurement

Impedance rheopneumography is a simple non-invasive technique that can reflect the vascular condition in the human pulmonary circulatory system. However, the much larger and almost in-banding respiratory artefact present has greatly restricted its usefulness to only respiratory patients of a less severe type, in view of the existing practice of requiring the subject to stop breathing momentarily during measurement. Conventional fixed or adaptive filtering cannot satisfactorily remove the artefact in view of the non-time stationary characteristic of the latter. In the paper, a fast adaptive FIR filter design method, which is based on the filter coefficient look-up table (CLT) concept, is presented as a solution. The CLT is constructed with the coefficients indexed to the cut-off frequency to separate the two components of the plethysmogram. An on-line fast Fourier transform is calculated to track the cut-off frequency. This filter can adaptively change its coefficients, not only for different subjects, but also for the same subject during long-term monitoring. Results show that this filter design is capable of providing an almost respiratory artefact-free signal for a majority of patients. The high speed of implementation also renders it a possibility for real-time monitoring applications.     

Family and Illness Predictors of Outcome in Pediatric Brain Tumors

Investigated the prediction of cognitive and behavioral outcomesin 63 children with heterogenous brain tumors. Hierarchicalmultiple regression analyses were used to determine how family-relatedvariables added to the prediction of children's outcome overand above illness measures. The best predictors of children'sbehavior problems and adaptive behavior were family and demographicvariables, whereas the best predictors of achievement were illnessand demographic variables. A combination of family and illnessvariables, however, was the best predictor of intellectual functioning.In addition to identifying specific predictors of cognitiveand behavioral outcome in children with brain tumors, theseresults lend initial support for the inclusion of contextualfactors such as family stress, maternal coping, number of parentsin the home, and family SES measures in studies of how diseasefactors affect outcomes in pediatric brain tumor patients.     

Changing contexts? The effects of a primary prevention program on classroom levels of peer relational and physical victimization

Whereas school‐based prevention programs often target deficits in individual children's social skills in order to limit their aggression or exposure to peer victimization, there is increasing evidence that school‐wide and classroom‐level factors can also affect the success of these programs. This short‐term longitudinal study involved 432 elementary school students from 44 classrooms in 17 urban schools. We investigated whether classroom characteristics (average levels of social competence, emotional problems, and behavioral problems) and school‐wide characteristics (proportion of children on income assistance and implementation of a peer victimization prevention program—the Walk away, Ignore, Talk, and Seek help [W.I.T.S.] program) experienced in Grade 1 influences changes in children's reports of relational and physical victimization at the end of Grade 2. Findings showed that classroom levels of emotional problems predicted increases in relational victimization (beyond individual differences in emotional and behavioral problems). Classroom levels of behavioral problems predicted reports of increases in physical victimization (beyond individual differences). Classroom levels of social competence also interacted with individual levels of emotional problems such that children with higher levels of emotional problems in classes with more socially competent children reported more relational and physical victimization. Higher school levels of poverty and lack of program involvement also predicted higher levels of physical victimization, beyond individual and classroom effects. The capacity of the W.I.T.S. program to influence classroom level characteristics and the moderating effects of school poverty on victimization were also assessed. © 2003 Wiley Periodicals, Inc. J Comm Psychol 31: 397–418, 2003.     

Measurement Issues in Emotion Research With Children and Adolescents

The need for a multimethod approach to the study of emotion in children and adolescents is crucial, as is a multilevel analysis in which emotional experience is assessed at a variety of levels (Solomon, 2002). This review highlights the critical role of emotion theory when constructing and selecting appropriate assessment tools with a focus on Functionalist theory that emphasizes the importance of contextual variables ( Barrett & Campos, 1987 ). The review begins with an examination of theoretical and pragmatic issues in emotion measurement followed by discussions of four basic methods of emotion assessment (i.e., self-report, other-report, observation, neurophysiology). Implications of emotion assessment for clinical practice and future directions for research conclude the review.     

Menstrual Cycle Phase is a Potential Confound in Psychophysiology Research

Effects of menstrual cycle phase on physiological levels and reactivity were studied in a withinsubject design with 20 women aged 18–30 years. Basal body temperature was monitored daily; follicular and luteal recording sessions occurred before and after the ovulatory temperature rise, respectively. The design consisted of task and rest periods, presented in counterbalanced order across phases. Half the subjects began during their follicular phase and half began during their luteal phase. Follicular and luteal phases were compared for differences between baseline resting levels, as well as for reactivity. The results showed menstrual phase differences in heart rate, pulse transit time, and EEG alpha, particularly during tasks, but no difference in reactivity. Habituation effects in the group that began during the follicular phase often masked luteal activation. In spite of the fact that not all statistical results achieved significance, the consistency of most trends supports the conclusion that physiological recording sessions with women might best be restricted to the follicular phase.